pH Signaling in Human Fungal Pathogens: a New Target for Antifungal Strategies

Cornet, Muriel; Gaillardin, Claude

doi:10.1128/ec.00313-13

Cited by 79 publications

(41 citation statements)

References 152 publications

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“…Since acidic pH-induced opaque cell formation is highly dependent on strain backgrounds and exhibits a relatively minor effect (compared to the effects of CO 2 and GlcNAc), we consider that pH may play an additive role in the environmental regulation of this phenotypic switching in C. albicans. The Rim101 pH-sensing pathway is highly conserved in pathogenic fungi (2,45). It has been shown that the rim101/rim101 mutant exhibits the defect of alkaline-induced hyphal growth (2,8).…”

Section: Discussionmentioning

confidence: 99%

pH Regulates White-Opaque Switching and Sexual Mating in Candida albicans

et al. 2015

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bAs a successful commensal and pathogen of humans, Candida albicans encounters a wide range of environmental conditions. Among them, ambient pH, which changes frequently and affects many biological processes in this species, is an important factor, and the ability to adapt to pH changes is tightly linked with pathogenesis and morphogenesis. In this study, we report that pH has a profound effect on white-opaque switching and sexual mating in C. albicans. Acidic pH promotes white-to-opaque switching under certain culture conditions but represses sexual mating. The Rim101-mediated pH-sensing pathway is involved in the control of pH-regulated white-opaque switching and the mating response. Phr2 and Rim101 could play a major role in acidic pH-induced opaque cell formation. Despite the fact that the cyclic AMP (cAMP) signaling pathway does not play a major role in pH-regulated white-opaque switching and mating, white and opaque cells of the cyr1/cyr1 mutant, which is defective in the production of cAMP, showed distinct growth defects under acidic and alkaline conditions. We further discovered that acidic pH conditions repressed sexual mating due to the failure of activation of the Ste2-mediated ␣-pheromone response pathway in opaque a cells. The effects of pH changes on phenotypic switching and sexual mating could involve a balance of host adaptation and sexual reproduction in C. albicans.

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Section: Discussionmentioning

confidence: 99%

pH Regulates White-Opaque Switching and Sexual Mating in Candida albicans

et al. 2015

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“…Indeed, the influence of pH has been linked to AF/ST production in Aspergillus species where pacC seems to be the key transcription factor involved in the response to pH [117] (Table 3). In addition, the PacC signaling pathway includes six other proteins with Pal domain, involved in pH sensing [118]. The transcription factor PacC is strongly expressed under alkaline conditions [117].…”

Section: Ph Conditionsmentioning

confidence: 99%

Aflatoxin Biosynthesis and Genetic Regulation: A Review

Caceres

Khoury

et al. 2020

Toxins

200

177

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The study of fungal species evolved radically with the development of molecular techniques and produced new evidence to understand specific fungal mechanisms such as the production of toxic secondary metabolites. Taking advantage of these technologies to improve food safety, the molecular study of toxinogenic species can help elucidate the mechanisms underlying toxin production and enable the development of new effective strategies to control fungal toxicity. Numerous studies have been made on genes involved in aflatoxin B1 (AFB1) production, one of the most hazardous carcinogenic toxins for humans and animals. The current review presents the roles of these different genes and their possible impact on AFB1 production. We focus on the toxinogenic strains Aspergillus flavus and A. parasiticus, primary contaminants and major producers of AFB1 in crops. However, genetic reports on A. nidulans are also included because of the capacity of this fungus to produce sterigmatocystin, the penultimate stable metabolite during AFB1 production. The aim of this review is to provide a general overview of the AFB1 enzymatic biosynthesis pathway and its link with the genes belonging to the AFB1 cluster. It also aims to illustrate the role of global environmental factors on aflatoxin production and the recent data that demonstrate an interconnection between genes regulated by these environmental signals and aflatoxin biosynthetic pathway.

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“…Compromising these pathways can reduce virulence, so they are being actively explored as antifungal targets (reviewed in [182]). The Pal pathway in Aspergillus nidulans has been extensively characterized [183] and shares many features with the S. cerevisiae Rim pathway.…”

Section: Proton Transport and Ph Control In Other Fungimentioning

confidence: 99%

Proton Transport and pH Control in Fungi

Kane

2016

Advances in Experimental Medicine and Biology

101

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Despite diverse and changing extracellular environments, fungi maintain a relatively constant cytosolic pH and numerous organelles of distinct lumenal pH. Key players in fungal pH control are V-ATPases and the P-type proton pump Pma1. These two proton pumps act in concert with a large array of other transporters and are highly regulated. The activities of Pma1 and the V-ATPaseare coordinated under some conditions, suggesting that pH in the cytosol and organelles is not controlled independently. Genomic studies, particularly in the highly tractable S. cerevisiae, are beginning to provide a systems-level view of pH control, including transcriptional responses to acid or alkaline ambient pH and definition of the full set of regulators required to maintain pH homeostasis. Genetically encoded pH sensors have provided new insights into localized mechanisms of pH control, as well as highlighting the dynamic nature of pH responses to the extracellular environment. Recent studies indicate that cellular pH plays a genuine signaling role that connects nutrient availability and growth rate through a number of mechanisms. Many of the pH control mechanisms found in S. cerevisiae are shared with other fungi, with adaptations for their individual physiological contexts. Fungi deploy certain proton transport and pH control mechanisms not shared with other eukaryotes; these regulators of cellular pH are potential antifungal targets. This re view describes current and emerging knowledge proton transport and pH control mechanisms in S. cerevisiae and briefly discusses how these mechanisms vary among fungi.

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pH Signaling in Human Fungal Pathogens: a New Target for Antifungal Strategies

Cited by 79 publications

References 152 publications

pH Regulates White-Opaque Switching and Sexual Mating in Candida albicans

pH Regulates White-Opaque Switching and Sexual Mating in Candida albicans

Aflatoxin Biosynthesis and Genetic Regulation: A Review

Proton Transport and pH Control in Fungi

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